What has Electron Microscopy Contributed to Alzheimer's Research?

References

• Association Alzheimer . 2014 Alzheimer's disease facts and figures. Alzheimers Dement.10(2), 47–92 (2014).
   Web of Science ®Google Scholar
• Dorsey ER , GeorgeBP, LeffB, WillisAW. The coming crisis: obtaining care for the growing burden of neurodegenerative conditions. Neurology80(21), 1989–1996 (2013).
   PubMed Web of Science ®Google Scholar
• Gatz M , ReynoldsCA, FratiglioniLet al. Role of genes and environments for explaining Alzheimer disease. Arch. Gen. Psychiatry63(2), 168–174 (2006).
   PubMed Web of Science ®Google Scholar
• van der Flier WM , SchoonenboomSN, PijnenburgYA, FoxNC, ScheltensP. The effect of APOE genotype on clinical phenotype in Alzheimer disease. Neurology67(3), 526–527 (2006).
   PubMed Web of Science ®Google Scholar
• Hardy JA , HigginsGA. Alzheimer's disease: the amyloid cascade hypothesis. Science256(5054), 184–185 (1992).
   PubMed Web of Science ®Google Scholar
• Tanzi RE , BertramL. Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell120(4), 545–555 (2005).
   PubMed Web of Science ®Google Scholar
• Maloney MT . One hundred years of Alzheimer's disease: the amyloid cascade hypothesis. Nat. Educ.8(4), 6 (2015).
   Google Scholar
• Goedert M , SpillantiniMG. A century of Alzheimer's disease. Science314(5800), 777–781 (2006).
   PubMed Web of Science ®Google Scholar
• Palop JJ , MuckeL. Amyloid-beta-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks. Nat. Neurosci.13(7), 812–818 (2010).
   PubMed Web of Science ®Google Scholar
• Matsumura A , EmotoMC, SuzukiSet al. Evaluation of oxidative stress in the brain of a transgenic mouse model of Alzheimer's disease by in vivo electron paramagnetic resonance imaging. Free Radic. Biol. Med.85, 165–173 (2015).
   PubMed Web of Science ®Google Scholar
• Mota SI , CostaRO, FerreiraILet al. Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease. Biochim. Biophys. Acta1852(7), 1428–1441 (2015).
   PubMed Web of Science ®Google Scholar
• Wang X , WangW, LiL, PerryG, LeeH-g, ZhuX. Oxidative stress and mitochondrial dysfunction in Alzheimer's disease. Biochim. Biophys. Acta1842(8), 1240–1247 (2014).
   PubMed Web of Science ®Google Scholar
• Shankar GM , LiS, MehtaTHet al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med.14(8), 837–842 (2008).
   PubMed Web of Science ®Google Scholar
• Baloyannis SJ . Oxidative stress and mitochondria alterations in Alzheimer's disease. Neurobiol. Aging21, 264 (2000).
   Google Scholar
• Baloyannis SJ , CostaV, MichmizosD. Mitochondrial alterations in Alzheimer's disease. Am. J. Alzheimers Dis. Other Dement.19(2), 89–93 (2004).
   PubMedGoogle Scholar
• Brosch JR , MatthewsBR. Journal club: comparison of symptomatic and asymptomatic persons with Alzheimer disease neuropathology. Neurology82(9), e76–e78 (2014).
   PubMed Web of Science ®Google Scholar
• Religa D , LaudonH, StyczynskaM, WinbladB, NäslundJ, HaroutunianV. Amyloid β pathology in Alzheimer's disease and schizophrenia. Am. J. Psychiatry160(5), 867–872 (2003).
   PubMed Web of Science ®Google Scholar
• Gouras GK , OlssonTT, HanssonO. β-amyloid peptides and amyloid plaques in Alzheimer's disease. Neurotherapeutics12(1), 3–11 (2015).
   PubMed Web of Science ®Google Scholar
• Mondragón‐Rodríguez S , PerryG, Luna‐MuñozJ, Acevedo-AquinoMC, WilliamsS. Phosphorylation of tau protein at sites Ser396–404 is one of the earliest events in Alzheimer's disease and Down syndrome. Neuropathol. Appl. Neurobiol.40(2), 121–135 (2014).
   PubMed Web of Science ®Google Scholar
• Hulette CM , Welsh-BohmerKA, MurrayMG, SaundersAM, MashDC, McIntyreLM. Neuropathological and neuropsychological changes in “normal” aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. J. Neuropathol. Exp. Neurol.57(12), 1168–1174 (1998).
   PubMed Web of Science ®Google Scholar
• Thal DR , FändrichM. Protein aggregation in Alzheimer's disease: Aβ and τ and their potential roles in the pathogenesis of AD. Acta Neuropathol.129(2), 163–165 (2015).
   PubMed Web of Science ®Google Scholar
• Sperling RA , DickersonBC, PihlajamakiMet al. Functional alterations in memory networks in early Alzheimer's disease. Neuromolecular Med.12(1), 27–43 (2010).
   PubMed Web of Science ®Google Scholar
• Ballatore C , LeeVM, TrojanowskiJQ. Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat. Rev. Neurosci.8(9), 663–672 (2007).
   PubMed Web of Science ®Google Scholar
• Neuman KM , Molina-CamposE, MusialTFet al. Evidence for Alzheimer's disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons. Brain Struct. Funct.220(6), 3143–3165 (2015).
   PubMed Web of Science ®Google Scholar
• Rekart JL , QuinnB, MesulamMM, RouttenbergA. Subfield-specific increase in brain growth protein in postmortem hippocampus of Alzheimer's patients. Neuroscience126(3), 579–584 (2004).
   PubMed Web of Science ®Google Scholar
• Mufson EJ , MahadyL, WatersD. Hippocampal plasticity during the progression of Alzheimer's disease. Neuroscience pii: S0306-4522(15)00221-3 (2015).
   PubMed Web of Science ®Google Scholar
• Zou C , MontagnaE, ShiYet al. Intraneuronal APP and extracellular Aβ independently cause dendritic spine pathology in transgenic mouse models of Alzheimer's disease. Acta Neuropath.129(6), 909–920 (2015).
   PubMed Web of Science ®Google Scholar
• Christensen DZ , HuettenrauchM, MitkovskiM, PradierL, WirthsO. Axonal degeneration in an Alzheimer mouse model is PS1 gene dose dependent and linked to intraneuronal Aβ accumulation. Front. Aging Neurosci.6, 139 (2014).
   PubMed Web of Science ®Google Scholar
• Kamphuis W , MiddeldorpJ, KooijmanLet al. Glial fibrillary acidic protein isoform expression in plaque related astrogliosis in Alzheimer's disease. Neurobiol. Aging35(3), 492–510 (2014).
   PubMed Web of Science ®Google Scholar
• Verkhratsky A , MarutleA, Rodríguez-ArellanoJJ, NordbergA. Glial asthenia and functional paralysis a new perspective on neurodegeneration and Alzheimer's disease. Neuroscientist pii: 10.3858414547132 (2014) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Baloyannis SJ , ManolidesSL, ManolidesLS. Dendritic and spinal pathology in the acoustic cortex in Alzheimer's disease: morphological estimation in Golgi technique and electron microscopy. Acta Otolaryngol.131(6), 610–612 (2011).
   PubMed Web of Science ®Google Scholar
• Baloyannis SJ , MavroudisI, MitilineosD, BaloyannisIS, CostaVG. The hypothalamus in Alzheimer's disease: a Golgi and Electron Microscope Study. Am. J. Alzheimers Dis. Other Demen.30(5), 478–487 (2015).
   PubMed Web of Science ®Google Scholar
• McKhann G , DrachmanD, FolsteinMet al. Clinical diagnosis of Alzheimer's disease: report of the NINCDSADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology34(7), 939–944 (1984).
   PubMed Web of Science ®Google Scholar
• Sperling RA , AisenPS, BeckettLAet al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement.7(3), 280–292 (2011).
   PubMed Web of Science ®Google Scholar
• Klunk WE , EnglerH, NordbergAet al. Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B. Annals Neurol.55(3), 306–319 (2004).
   PubMed Web of Science ®Google Scholar
• Viola KL , SbarboroJ, SurekaRet al. Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease. Nat. Nanotechnol.10(1), 91–98 (2015).
   PubMed Web of Science ®Google Scholar
• Fagan AM . CSF biomarkers of Alzheimer's disease: impact on disease concept, diagnosis, and clinical trial design. Adv. Geriatr.2014, 302712 (2014).
   Google Scholar
• Lehmann S , SchraenS, QuadrioI. Impact of harmonization of collection tubes on Alzheimer's disease diagnosis. Alzheimers Dement.10(5), S390–S394 (2014).
   PubMed Web of Science ®Google Scholar
• Molinuevo JL , BlennowK, DuboisBet al. The clinical use of cerebrospinal fluid biomarker testing for Alzheimer's disease diagnosis: a consensus paper from the Alzheimer's biomarkers standardization initiative. Alzheimers Dement.10(6), 808–817 (2014).
   PubMed Web of Science ®Google Scholar
• Fagan AM , MintunMA, ShahARet al. Cerebrospinal fluid tau and ptau (181) increase with cortical amyloid deposition in cognitively normal individuals: implications for future clinical trials of Alzheimer's disease. EMBO Mol. Med.1(8–9), 371–380 (2009).
   PubMed Web of Science ®Google Scholar
• Gallyas G , HsuM, BuzsakiG. Four modified silver methods for thick sections of formaldehyde-fixed mammalian central nervous tissue: ‘dark’ neurons, perikarya of all neurons, microglial cells and capillaries. J. Neurosci. Methods50, 159–164 (1993).
   PubMed Web of Science ®Google Scholar
• Baloyannis SJ . Dendritic pathology in Alzheimer's disease. J. Neurol. Sci.283(1–2), 153–157 (2009).
   PubMedGoogle Scholar
• Baloyannis SJ , BaloyannisJS. The vascular factor in Alzheimer's disease: a study in Golgi technique and electron microscopy. J. Neurol. Sci.322(1–2), 117–121 (2012).
   PubMed Web of Science ®Google Scholar
• Braak H , BraakE. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol.82(4), 239–259 (1991).
   PubMed Web of Science ®Google Scholar
• Golgi C . Sulla struttura della sostanza grigia del cervello. Gazz. Med. Ita. Lombarda33, 244–246 (1873).
   Google Scholar
• Scheibel ME , ScheibelAB. The methods of Golgi. In: Neuroanatomical Research Techniques. RobertsonRT ( Ed.). Academic PressNY, USA, 90–114 (1978).
   Google Scholar
• Baloyannis SJ . Staining of dead neurons by the Golgi method in autopsy material. Methods Mol. Biol.1254, 167–179 (2015).
   PubMedGoogle Scholar
• Baloyannis SJ . Staining neurons with Golgi techniques in degenerative diseases of the brain. Neural Regen. Res.10(5), 693–695 (2015).
   PubMed Web of Science ®Google Scholar
• Schmued LC , StowersCC, ScalletAC, XuL. Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons. Brain Res.1035(1), 24–31 (2005).
   PubMed Web of Science ®Google Scholar
• Cavrieli Y , ShermanY, Ben-SassonSA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol.119(3), 493–501 (1992).
   PubMed Web of Science ®Google Scholar
• Danscher G , ZimmerJ. An improved timm sulphide silver method for light and electron microscopic localization of heavy metals in biological tissues. Histochemistry55(1), 27–40 (1978).
   PubMedGoogle Scholar
• Noraberg J , KristensenBW, ZimmerJ. Markers for neuronal degeneration in organotypic slice cultures. Brain Res. Brain Res. Protoc.3(3), 278–290 (1999).
   PubMedGoogle Scholar
• Kidd M . Paired helical filaments in electron microscopy of Alzheimer's disease. Nature197, 192–193 (1963).
   PubMed Web of Science ®Google Scholar
• Kidd M . Alzheimer's disease-an electron microscopical study. Brain87(2), 307–320 (1964).
   PubMed Web of Science ®Google Scholar
• Hales CM , DammerEB, DinerI. Aggregates of small nuclear ribonucleic acids (snRNAs) in Alzheimer's disease. Brain Pathol.24(4), 344–351 (2014).
   PubMed Web of Science ®Google Scholar
• Baloyannis SJ . Recent progress of the Golgi technique and electron microscopy to examine dendritic pathology in Alzheimer's disease. Future Neurol.8, 239–242 (2013).
   Google Scholar
• Fiala JC , SpacekJ, HarrisKM. Dendritic spine pathology: cause or consequence of neurological disorders?Brain Res. Rev.39(1), 29–54 (2002).
   PubMedGoogle Scholar
• Baloyannis SJ . Morphological and morphometric alterations of Cajal–Retzius cells in early cases of Alzheimer's disease: a Golgi and electron microscope study. Intern. J. Neurosci.115(7), 965–980 (2005).
   PubMed Web of Science ®Google Scholar
• Westrate LM , LeeJE, PrinzWA, VoeltzGK. Form follows function: the importance of endoplasmic reticulum shape. Annu. Rev. Biochem.84, 791–811 (2015).
   PubMed Web of Science ®Google Scholar
• Xu L-H , XieH, ShiZ-Het al. Critical role of endoplasmic reticulum stress in chronic intermittent hypoxia-induced deficits in synaptic plasticity and long-term memory. Antioxid. Redox Signal.23(9), 695–710 (2015).
   PubMed Web of Science ®Google Scholar
• Hales CM , SeyfriedNT, DammerEBet al. U1 small nuclear ribonucleoproteins (snRNPs) aggregate in Alzheimer's disease due to autosomal dominant genetic mutations and trisomy 21. Mol. Neurodegener.9, 15 (2014).
   PubMed Web of Science ®Google Scholar
• Rambaran RN , SerpellLC. Amyloid fibrils abnormal protein assembly. Prion2(3), 112–117 (2008).
   PubMed Web of Science ®Google Scholar
• Hossain S , HashimotoM, KatakuraM, Al MamunA, ShidoO. Medicinal value of asiaticoside for Alzheimer's disease as assessed using single-molecule-detection fluorescence correlation spectroscopy, laser-scanning microscopy, transmission electron microscopy, and in silico docking. BMC Complem. Altern. Med.15(1), 1–14 (2015).
   PubMedGoogle Scholar
• DeKosky ST , ScheffSW. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann. Neurol.27(5), 457–464 (1990).
   PubMed Web of Science ®Google Scholar
• Salminen A , HaapasaloA, KauppinenA, KaarnirantaK, SoininenH, HiltunenM. Impaired mitochondrial energy metabolism in Alzheimer's disease: impact on pathogenesis via disturbed epigenetic regulation of chromatin landscape. Prog. Neurobiol.131, 1–20 (2015).
   PubMed Web of Science ®Google Scholar
• Placido AI , PereiraCM, DuarteAIet al. The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implication's for Alzheimer's disease. Biochim. Biophys. Acta1842(9), 1444–1453 (2014).
   PubMed Web of Science ®Google Scholar
• Anandatheerthavarada HK , BiswasG, RobinMA, AvadhaniNG. Mitochondrial targeting and a novel transmembrane arrest of Alzheimer's amyloid precursor protein impairs mitochondrial function in neuronal cells. J. Cell Biol.161(1), 41–54 (2003).
   PubMed Web of Science ®Google Scholar
• Pagani L , EckertA. Amyloid-beta interaction with mitochondria. Internl. J. Alzh. Dis.2011, 925050 (2011).
   PubMedGoogle Scholar
• Hansson CA , FryckmanS, FarmeryMet al. Nicastrin, presenilin, APH-1, and PEN-2 form active γ-secretase complexes in mitochondria. J. Biol. Chem.279(49), 51654–51660 (2004).
   PubMed Web of Science ®Google Scholar
• Wolfe MS . Unlocking truths of γ-secretase in Alzheimer's disease: what is the translational potential?Future Neurol.9(4), 419–429 (2014).
   PubMedGoogle Scholar
• Arias C , MontielT, Quiroz-BaezR, MassieuL. Beta-amyloid neurotoxicity is exacerbated during glycolysis inhibition and mitochondrial impairment in the rat hippocampus in vivo and in isolated nerve terminals: implications for Alzheimer's disease. Expr. Neurol.176(1), 163–74 (2002).
   PubMed Web of Science ®Google Scholar
• Wu Z , ZhuY, CaoX, SunS, ZhaoB. Mitochondrial toxic effects of Aβ through mitofusins in the early pathogenesis of Alzheimer's disease. Mol. Neurobiol.50(3), 986–996 (2014).
   PubMed Web of Science ®Google Scholar
• Greenough MA , CamakarisJ, BushAI. Metal dyshomeostasis and oxidative stress in Alzheimer's disease. Neurochem. Int.62(5), 540–55 (2013).
   PubMed Web of Science ®Google Scholar
• Perry G , NunomuraA, HiraiK, TakedaA, AlievG, SmithM. Oxidative damage in Alzheimer's disease: the metabolic dimension. Intern. J. Developm. Neurosci.18(4–5), 417–421 (2000).
   PubMed Web of Science ®Google Scholar
• Schuh RA , JacksonKC, SchlappalAE. Mitochondrial oxygen consumption deficits in skeletal muscle isolated from an Alzheimer's disease-relevant murine model. BMC Neurosci.15, 24 (2014).
   PubMed Web of Science ®Google Scholar
• Gadd ME , BroekemeierKM, CrouserED, KumarJ, GraffG, PfeifferDR. Mitochondrial iPLA2 activity modulates the release of cytochrome c from mitochondria and influences the permeability transition. J. Biol. Chem.281(11), 6931–6939 (2006).
   PubMed Web of Science ®Google Scholar
• Kinghorn KJ , Castillo-QuanJI, BartolomeFet al. Loss of PLA2G6 leads to elevated mitochondrial lipid peroxidation and mitochondrial dysfunction. Brain138(7), 1801–1816 (2015).
   PubMedGoogle Scholar
• Strokin M , SeburnKL, CoxGA, MartensKA, ReiserG. Severe disturbance in the Ca2 + signaling in astrocytes from mouse models of human infantile neuroaxonal dystrophy with mutated Pla2g6. Hum. Mol. Genet.21(12), 2807–2814 (2012).
   PubMed Web of Science ®Google Scholar
• McNeill A . PLA2G6 mutations and other rare causes of neurodegeneration with brain iron accumulation. Curr. Drug Targets13(9), 1204–1206 (2012).
   PubMed Web of Science ®Google Scholar
• Baloyannis SJ . Mitochondrial and golgi apparatus’ alterations in Alzheimer's disease: a study of the cerebellar cortex based on silver impregnation technique and electron microscopy. In: Frontiers in Clinical Drug Research - Alzheimer Disorders Vol. 2. Atta-ur-Rahman ( Ed.). Bentham Science Publishers, Emirate of Sharjah, 3–27 (2014).
   Google Scholar
• Baloyannis SJ . Mitochondria and Alzheimer's disease. J. Neurol. Stroke1, 5 (2014).
   Google Scholar
• Stewart P , HayakawaK, AkersM, VintersH. A morphometric study of the blood-brain barrier in Alzheimer's disease. Lab. Invest.67(6), 734–42 (1992).
   PubMed Web of Science ®Google Scholar
• Peterson C , GolmanJE. Alterations in calcium content and biochemical processes in cultured skin fibroblasts from aged and Alzheimer donors. Proc. Natl Acad. Sci. USA83(8), 2758–2762 (1986).
   PubMed Web of Science ®Google Scholar
• Podlesniy P1 , Figueiro-SilvaJ, LladoAet al. Low cerebrospinal fluid concentration of mitochondrial DNA in preclinical Alzheimer disease. Ann. Neurol.74(5), 655–668 (2013).
   PubMed Web of Science ®Google Scholar
• Twig G1 , ElorzaA, MolinaAJet al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J.27(2), 433–446 (2008).
   PubMed Web of Science ®Google Scholar
• Chen H , McCafferyJM, ChanDC. Mitochondrial fusion protects against neurodegeneration in the cerebellum. Cell130(3), 548–562 (2007).
   PubMed Web of Science ®Google Scholar
• Frezza C , CipolatS, Martins de BritoOet al. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell126(1), 177–189 (2006).
   PubMed Web of Science ®Google Scholar
• Kowald A , KirkwoodTBL. Evolution of the mitochondrial fusion–fission cycle and its role in aging. Proc. Natl Acad. Sci. USA108(25), 10237–10242 (2011).
   PubMed Web of Science ®Google Scholar
• Miller KE , SheetzMP. Axonal mitochondrial transport and potential are correlated. J. Cell Sci.117(Pt 13), 2791–2804 (2004).
   PubMed Web of Science ®Google Scholar
• Yao J , IrwinR, ChenS, HamiltonR, CadenasE, BrintonRD. Ovarian hormone loss induces bioenergetic deficits and mitochondrial β-amyloid. Neurobiol. Aging33(8), 1507–1521 (2012).
   PubMed Web of Science ®Google Scholar
• Simpkins JW , DykensJA. Mitochondrial mechanisms of estrogen neuro-protection. Brain Res. Rev.57(2), 421–430 (2008).
   PubMedGoogle Scholar
• Baloyannis S . The Golgi apparatus of Purkinje cells in Alzheimer's disease. In: Neuropathology Back to the Roots. BohlJ ( Ed.). Shaker Vertag, Aachen, Germany, 1–10 (2002).
   Google Scholar
• Stieber A , MourelatosZ, GonatasNK. In Alzheimer's disease the Golgi Apparatus of a population of neurons without neurofibrillary tangles is fragmented and atrophic. Am. J. Pathol.148(2), 415–426 (1996).
   PubMed Web of Science ®Google Scholar
• Baloyannis SJ . Golgi apparatus and protein trafficking in Alzheimer's disease. J. Alzheimers Dis.42(Suppl. 3), 153–162 (2014).
   Google Scholar
• Agostinhoa P , PliássovaaA, OliveiraaCR, CunhaaRA. Localization and trafficking of amyloid-protein precursor and secretases: impact on Alzheimer's disease. J. Alzheimers Dis.45(2), 329–347 (2015).
   PubMed Web of Science ®Google Scholar
• Haass C , KaetherC, ThinakaranG, SisodiaS. Trafficking and proteolytic processing of APP. Cold Spring Harb. Perspect. Med.2(5), a006270 (2012).
   PubMed Web of Science ®Google Scholar
• Hammerschlag R , StoneGC, BolenFA, LindseyJD, EllismanMH. Evidence that all newly synthesized proteins destined for fast axonal transport pass through the Golgi apparatus. J. Cell Biol.93(3), 568–575 (1982).
   PubMed Web of Science ®Google Scholar
• Thinakaran G , KooEH. Amyloid precursor protein trafficking, processing, and function. J. Biol. Chem.283(44), 29615–29619 (2008).
   PubMed Web of Science ®Google Scholar
• Golgi C . Intorno alla struttura delle cellule nervose. Bollettino della Società Medico Chirurgica di Pavia13, 3–16 (1898).
   Google Scholar
• Bentivoglio M . The discovery of the Golgi apparatus. J. Hist. Neurosci.8(2), 202–208 (1999).
   PubMedGoogle Scholar
• Gonatas NK . Rous-Whipple award lecture. Contribution to the physiology and pathology of the Golgi apparatus. Am. J. Pathol.145(4), 751–761 (1994).
   PubMed Web of Science ®Google Scholar
• Griffiths G , SimonsK. The trans Golgi network: sorting at the exit site of the Golgi complex. Science234(4775), 438–443 (1986).
   PubMed Web of Science ®Google Scholar
• Kienzle C , von BlumeJ. Secretory cargo sorting at the trans-Golgi network. Trends Cell. Biol.24(10), 584–593 (2014).
   PubMed Web of Science ®Google Scholar
• Bonifacino JS , RojasR. Retrograde transport from endosomes to the trans-Golgi network. Nat. Rev. Mol. Cell Biol.7(8), 568–579 (2006).
   PubMed Web of Science ®Google Scholar
• Burd CG . Physiology and pathology of endosome-to-Golgi retrograde sorting. Traffic12(8), 948–955 (2011).
   PubMed Web of Science ®Google Scholar
• Baloyannis SJ . Alterations of mitochondria and Golgi apparatus are related to synaptic pathology in Alzheimer's disease. In: Neurodegenerative Diseases. KishoreU ( Ed.). InTech Rijeka, Croatia, 101–123 (2013).
   Google Scholar
• De Matteis , AntoniettaM, RegaLR. Endoplasmic reticulum–Golgi complex membrane contact sites. Curr. Opin. Cell Biol.35, 43–50 (2015).
   PubMed Web of Science ®Google Scholar
• Baloyannis SJ , ManolidisSL, ManolidisLS. The acoustic cortex in Alzheimer's disease. Acta Oto-Laryngologica Suppl.494, 1–13 (1992).
   Google Scholar
• Baloyannis SJ . Golgi apparatus in Alzheimer's disease. J. Neurol. Stroke2, 3 (2015).
   Google Scholar
• van Dis V , KuijpersM, HaasdijkEDet al. Golgi fragmentation precedes neuromuscular denervation and is associated with endosome abnormalities in SOD1-ALS mouse motor neurons. Acta Neuropathol. Commun.2, 38 (2014).
   PubMed Web of Science ®Google Scholar
• Deatherage CL , HadziselimovicA, SandersCR. Purification and characterization of the human γ-secretase. Activ. Prot. Biochem.51(25), 5153–5159 (2012).
   Google Scholar
• Borgegard T , JureusA, OlssonFet al. First and second generation gamma-secretase modulators (GSMs) modulate Abeta production through different mechanisms. J. Biol. Chem.287(15), 11810–11819 (2012).
   PubMed Web of Science ®Google Scholar
• Chu J , LiJG, JoshiYB, GiannopoulosPF, HoffmanNE, MadeshM, PraticòD. Gamma secretase-activating protein is a substrate for Caspase-3: implications for Alzheimer's disease. Biol. Psychiatry77(8), 720–728 (2015).
   PubMed Web of Science ®Google Scholar
• Obermoeller-McCormick LM , LiY, OsakaH, FitzGeraldDJ, SchwartzAL, BuG. Dissection of receptor folding and ligand-binding property with functional mini receptors of LDL receptor-related protein. J. Cell Sci.114(Pt 5), 899–908 (2001).
   PubMed Web of Science ®Google Scholar
• Mikhailenko I , BatteyFD, MiglioriniMet al. Recognition of alpha 2-macroglobulin by the low density lipoprotein receptor-related protein requires the cooperation of two ligand binding cluster regions. J. Biol. Chem.276(42), 39484–39491 (2001).
   PubMed Web of Science ®Google Scholar
• Annaert WG , LevesqueL, CraessaertsKet al. Presenilin 1 controls gamma-secretase processing of amyloid precursor protein in pre-Golgi compartments of hippocampal neurons. J. Cell Biol.147(2), 277–294 (1999).
   PubMed Web of Science ®Google Scholar
• Georgakopoulos A , MarambaudP, FriedrichVLJr,ShioiJ, EfthimiopoulosS, RobakisNK. Presenilin-1: a component of synaptic and endothelial adherens junctions. Ann. NY Acad. Sci.920, 209–214 (2000).
   PubMed Web of Science ®Google Scholar
• Schedin-Weiss S , WinbladB, TjernbergLO. The role of protein glycosylation in Alzheimer disease. FEBS J.281(1), 46–62 (2014).
   PubMed Web of Science ®Google Scholar
• McFarlane I , GeorgopoulouN, CoughlanCM, GillianAM, BreenKC. The role of the protein glycosylation state in the control of cellular transport of the amyloid β precursor protein. Neuroscience90(1), 15–25 (1999).
   PubMed Web of Science ®Google Scholar
• Szebenyi G , BollatiF, BisbalMet al. Activity-driven dendritic remodeling requires microtubule associated protein 1A. Curr. Biol.15(20), 1820–1826 (2005).
   PubMed Web of Science ®Google Scholar
• Falke E , NissanovJ, MitchelTW, BennetDA, TrojanowskiJO, ArnoldSE. Subiculum dendritic arborization in Alzheimer's disease correlates with neurofibrillary tangle density. Am. J. Pathol.163(4), 1615–1631 (2006).
   Google Scholar
• Nyengaard JR , GundersenHJ. Direct and efficient stereological estimation of total cell quantities using electron microscopy. J. Microsc.222(pt 3), 182–187 (2006).
   PubMedGoogle Scholar
• West MJ . The precision of estimates in stereological analyses. Cold Spring Harb. Protoc.2012(9), 937–949 (2012).
   PubMedGoogle Scholar
• Small JV . Measurement of section thickness. Proceedings of the 4th European Congress on Electron Microscopy. Vol. 1. Tipografia Poliglotta Vaticana Rome. 609–610 (1968).
   Google Scholar
• Sterio DC . The unbiased estimation of number and sizes of arbitrary particles using the disector. J. Microsc.134(Pt 2), 127–136 (1984).
   PubMed Web of Science ®Google Scholar
• Ebrahimi S , OkabeS. Structural dynamics of dendritic spines: molecular composition, geometry and functional regulation. Biochim. Biophys. Acta1838(10), 2391–2398 (2014).
   PubMed Web of Science ®Google Scholar
• Baddeley AJ , GundersenHJG, Cruz OriveLM. Estimation of surface area from vertical sections. J. Microsc.142(3), 259–276 (1986).
   PubMedGoogle Scholar
• Šišková Z , JustusD, KanekoHet al. Dendritic structural degeneration is functionally linked to cellular hyperexcitability in a mouse model of Alzheimer's disease. Neuron84(5), 1023–1033 (2014).
   PubMed Web of Science ®Google Scholar
• Scheff SW , PriceDA, AnsariMAet al. Synaptic change in the posterior cingulate gyrus in the progression of Alzheimer's disease. J. Alzheimers Dis.43(3), 1073–1090 (2015).
   PubMed Web of Science ®Google Scholar
• Baloyannis SJ . Mitochondria are related to synaptic pathology in Alzheimer's disease. Int. J. Alzheimers Dis.2011, 305395 (2011).
   PubMedGoogle Scholar
• Kirkwood CM , CiuchtaJ, IkonomovicMDet al. Dendritic spine density, morphology, and fibrillar actin content surrounding amyloid-[beta] plaques in a mouse model of amyloid-[beta] deposition. J. Neuropathol. Exp. Neurol.72(8), 791–800 (2013).
   PubMed Web of Science ®Google Scholar
• Mavroudis IA , FotiouDF, MananiMGet al. Dendritic pathology and spinal loss in the visual cortex in Alzheimer's disease: a Golgi study in pathology. Int. J. Neurosci.121(7), 347–354 (2011).
   PubMed Web of Science ®Google Scholar
• Winkler EA , SagareAP, ZlokovicBV. The pericyte: a forgotten cell type with important implications for Alzheimer's disease?Brain Pathol.24(4), 371–386 (2014).
   PubMed Web of Science ®Google Scholar
• Gates G , BeiserA, ReesTS, D'AgostinoR, WolfP. Central auditory dysfunction may precede the onset of clinical dementia in people with probable Alzheimer's disease. J. Am. Ger. Soc.50(3), 482–488 (2002).
   PubMed Web of Science ®Google Scholar
• Neuman KM , Molina-CamposE, MusialTFet al. Evidence for Alzheimer's disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons. Brain Struct. Funct.220(6), 3143–3165 (2015).
   PubMed Web of Science ®Google Scholar
• Morrison JH , BaxterMG. The ageing cortical synapse: hallmarks and implications for cognitive decline. Nat. Rev. Neurosci.13(4), 240–250 (2012).
   PubMed Web of Science ®Google Scholar
• Tai H-C , WangBY, PozoAS, FroschMP, Spires-JonesTL, HymanBT. Frequent and symmetric deposition of misfolded tau oligomers within presynaptic and postsynaptic terminals in Alzheimer's disease. Neuropath. Commun.2(1), 146 (2014).
   PubMedGoogle Scholar
• Kamat PK , KalaniA, GivvimaniS, SathnurPB, TyagiSC, TyagiN. Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice. Neuroscience252, 302–319 (2013).
   PubMed Web of Science ®Google Scholar
• Tyagi N , OvechkinAV, LominadzeD, MoshalKS, TyagiSC. Mitochondrial mechanism of microvascular endothelial cells apoptosis in hyperhomo–cysteinemia. J. Cell Biochem.98(5), 1150–1162 (2006).
   PubMed Web of Science ®Google Scholar
• Gasche Y , FujimuraM, Morita-FujimuraYet al. Early appearance of activated matrix metalloproteinase-9 after focal cerebral ischemia in mice: a possible role in blood–brain barrier dysfunction. J. Cereb. Blood Flow Metab.19, 1020–1028 (1999).
   PubMed Web of Science ®Google Scholar
• Koffie RM , HashimotoT, TaiHCet al. Apolipoprotein E4 effects in Alzheimer's disease are mediated by synaptotoxic oligomeric amyloid-β. Brain135(Pt 7), 2155–2168 (2012).
   PubMedGoogle Scholar
• Halliday MR , RegeSV, MaQet al. Accelerated pericyte degeneration and blood–brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease. J. Cereb. Blood Flow Metab. doi: 10.1038/jcbfm.2015.44 (2015) ( Epub ahead of print).
   Web of Science ®Google Scholar
• Kalaria RN , PaxAB. Increased collagen content of cerebral microvessels in Alzheimer's disease. Brain Res.705(1–2), 349–352 (1995).
   PubMed Web of Science ®Google Scholar
• Breteler MM . Vascular risk factors for Alzheimer's disease: an epidemiologic perspective. Neurobiol. Aging21(2), 153–160 (2000).
   PubMed Web of Science ®Google Scholar
• Gupta A , IadecolaC. Impaired Aβ clearance: a potential link between atherosclerosis and Alzheimer's disease. Front. Aging Neurosci.7, 115 (2015).
   PubMed Web of Science ®Google Scholar